1. Developmental Biology
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Extracellular interactions and ligand degradation shape the Nodal morphogen gradient

  1. Yin Wang
  2. Xi Wang
  3. Thorsten Wohland
  4. Karuna Sampath  Is a corresponding author
  1. University of Warwick, United Kingdom
  2. National University of Singapore, Singapore
Research Article
  • Cited 24
  • Views 2,322
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Cite this article as: eLife 2016;5:e13879 doi: 10.7554/eLife.13879

Abstract

The correct distribution and activity of secreted signaling proteins called morphogens is required for many developmental processes. Nodal morphogens play critical roles in embryonic axis formation in many organisms. Models proposed to generate the Nodal gradient include diffusivity, ligand processing, and a temporal activation window. But how the Nodal morphogen gradient forms in vivo remains unclear. Here, we have measured in vivo for the first time, the binding affinity of Nodal ligands to their major cell surface receptor, Acvr2b, and to the Nodal inhibitor, Lefty, by fluorescence cross-correlation spectroscopy. We examined the diffusion coefficient of Nodal ligands and Lefty inhibitors in live zebrafish embryos by fluorescence correlation spectroscopy. We also investigated the contribution of ligand degradation to the Nodal gradient. We show that ligand clearance via degradation shapes the Nodal gradient and correlates with its signaling range. By computational simulations of gradient formation, we demonstrate that diffusivity, extra-cellular interactions, and selective ligand destruction collectively shape the Nodal morphogen gradient.

Article and author information

Author details

  1. Yin Wang

    Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Xi Wang

    Department of Chemistry, Centre for Bioimaging Sciences, National University of Singapore, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  3. Thorsten Wohland

    Department of Biological Sciences, National University of Singapore, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  4. Karuna Sampath

    Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom
    For correspondence
    K.Sampath@warwick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with institutional animal care regulations and protocols of the National University of Singapore and the University of Warwick (PPL number 70/7836 and PIL number 70/26057 to KS).

Reviewing Editor

  1. Didier Y R Stainier, Max Planck Institute for Heart and Lung Research, Germany

Publication history

  1. Received: December 17, 2015
  2. Accepted: April 20, 2016
  3. Accepted Manuscript published: April 21, 2016 (version 1)
  4. Version of Record published: May 31, 2016 (version 2)

Copyright

© 2016, Wang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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